Disarming, combating a tropical parasite.

The parasites responsible for the devastating skin ulcers of the tropical disease leishmaniasis use one of the body's own chemicals to evade destruction by the immune system, according to a new study. A second report suggests that extremely low doses of a Leishmania parasite might serve as a vaccine to prime the body's defenses against this marauder.

The World Health Organization estimates that Leishmania microorganisms currently infect 12 million people worldwide, from the jungles of India and the Amazon basin to the deserts of northern Africa. Spread by several species of blood-sucking sand flies, these protozoans cause disfiguring open sores at the sites of infection. In some cases, the parasites migrate to internal organs such as the liver and spleen. This causes a potentially fatal, wasting disease named kala-azar - Hindi for "black sickness," so called because of the victims' darkening skin.

Ironically Leishmania wreaks its devastation by infecting macrophages, white blood cells that normally gobble up and digest bacteria and other microorganisms. In one new study, a group led by Steven G. Reed of the Seattle Biomedical Research institute found that the parasites survive the hostile environment inside macrophages by prompting the cells to produce large amounts of transforming growth factorbeta (TGF-beta). Macrophages normally make this chemical after they have eradicated an infection, in order to neutralize the bleach-like compound they use to kill microbes.

Reed and his colleagues report in the July 24 Science that injections of TGF-beta rendered normally resistant strains of mice susceptible to ulcers caused by Leishmania. Moreover, they found that injections of antibodies that block TGF-beta helped the mice fend off preexisting Leishmania infections.

"We think that TGF-beta production is a very early event in Leishmania infection," concludes Reed. "Basically, the parasite has figured out a way to keep the macrophages from killing it."

Reed says his group is now evaluating several chemical compounds that either block TGF-beta or prevent its production. He hopes to use these compounds in a cream to eliminate the skin ulcers of leishmaniasis. Currently, the only treatment for leishmaniasis is a salt made from the toxic metal antimony, which has dangerous side effects and must be taken intravenously every day for several weeks.

David L. Sacks, a leishmaniasis researcher at the National Institute of Allergy and Infectious Diseases in Bethesda, Md., says the study by Reed's group represents the first time researchers have successfully combated an ongoing leishmaniasis infection with a drug other than antimony. "This is extraordinary," says Sacks. "It has important implications for developing better treatments for this disease:"

In a separate study, a group led by Peter A. Bretscher at the University of Saskatchewan in Saskatoon evaluated a potential vaccine against leishmaniasis. Bretscher and his colleagues found that they could protect susceptible mice from subsequent Leishmania infection by inoculating them with 330 to 1,000 live parasites.

In the July 24 Science, Bretscher's group reports that such low doses of parasites raised the number of white blood cells in the mice without actually causing disease. Sacks, however, remains skeptical. "I don't understand how this could work," he says, because sand flies often transmit leishmaniasis by transferring fewer parasites than the number in the Canadian team's vaccine.